Prefunctionalised PLGA microparticles with dimethylaminoethyl moieties promote surface cell adhesion at physiological condition

Abstract

Synthetic hydrolytically degradable polyesters have seen widespread translation into a variety of clinical and biomedical settings; finding use as cell culture systems, drug delivery systems, tissue repair scaffolds, and medical devices. This success is owed in part due to their biocompatible nature and tuneable degradation profile. However, the lack of adhesion moieties limits the capacity of the polyesters to interact with cellular material and as such hampers their effectiveness within these applications. Several physical and chemical post-modification techniques have been developed to insert adhesion moieties; however, the nature of these methods remains complex and troublesome for translational medicine. To combat this flaw, we present a novel prefunctionalization method for the generation of poly (lactic-co-glycolic acid) PLGA microparticles with integrated adhesion moieties as a proof-of-principle. This strategy promotes surface cell adhesion at physiological conditions without the requirement for further post-modification. The basis of the prefunctionalization method was to utilise the 2-2-dimethylaminoethanol as an initiator in a standard bulk Ring Opening Polymerization process to obtain PLGADMAE polymers. The resultant polymers were subsequently used in the fabrication of the microparticles, via membrane emulsion. This process allowed control over the morphology and size distribution of the microparticles. The surface cell adhesive properties of the new PLGADMAE microparticles were investigated via co-culture with Adipose-Derived Stem Cells. Scanning Electron Microscopy showed that the new PLGADMAE microparticles readily promote adhesion of the ADSCs at physiological conditions. LDH and LIVE/DEAD assays demonstrated that the surface functionalised PLGADMAE microparticles maintained a low toxicity profile compared to the unmodified PLGA microparticles. Both thermogravimetric and differential scanning calorimetric analysis confirmed that the bulk properties of the polymer remained unchanged compared to the control PLGA. Gel Permeation Chromatography and Scanning Electron Microscopy imaging showed that the degradation profile of the new PLGADMAE was enhanced compared to that of standard PLGA polymers. This novel prefunctionalization strategy eliminates the need for post-modification and could evolve rapidly to develop biodegradable biomaterials with enhanced cell adhesion and tuneable surface chemistry to allow greater control and/or maintain interaction with living cells and tissues. The implication of this new approach would be far reaching in the field of cell delivery, cell expansion, tissue engineering and regenerative medicine.